A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using ...a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
An accurate description of nonadiabatic energy relaxation is crucial for modeling atomistic dynamics at metal surfaces. Interfacial energy transfer due to electron-hole pair excitations coupled to ...motion of molecular adsorbates is often simulated by Langevin molecular dynamics with electronic friction. Here, we present calculations of the full electronic friction tensor by using first order time-dependent perturbation theory at the density functional theory level. We show that the friction tensor is generally anisotropic and nondiagonal, as found for hydrogen atom on Pd(100) and CO on Cu(100) surfaces. This implies that electron-hole pair induced nonadiabatic coupling at metal surfaces leads to friction-induced mode coupling, therefore, opening an additional channel for energy redistribution. We demonstrate the robustness and accuracy of our results by direct comparison to established methods and experimental data.
Piezo ion channels are activated by various types of mechanical stimuli and function as biological pressure sensors in both vertebrates and invertebrates. To date, mechanical stimuli are the only ...means to activate Piezo ion channels and whether other modes of activation exist is not known. In this study, we screened ~3.25 million compounds using a cell-based fluorescence assay and identified a synthetic small molecule we termed Yoda1 that acts as an agonist for both human and mouse Piezo1. Functional studies in cells revealed that Yoda1 affects the sensitivity and the inactivation kinetics of mechanically induced responses. Characterization of Yoda1 in artificial droplet lipid bilayers showed that Yoda1 activates purified Piezo1 channels in the absence of other cellular components. Our studies demonstrate that Piezo1 is amenable to chemical activation and raise the possibility that endogenous Piezo1 agonists might exist. Yoda1 will serve as a key tool compound to study Piezo1 regulation and function.
The current study investigated whether mindfulness and psychological flexibility uniquely and separately accounted for variability in psychological distress (somatization, depression, anxiety, and ...general psychological distress). An ethnically diverse, nonclinical sample of college undergraduates (N = 494, 76% female) completed a Web-based survey that included the self-report measures of interest. Consistent with prior research, psychological flexibility and mindfulness were positively associated with each other, and tested separately, both variables were negatively associated with somatization, depression, anxiety, and general psychological distress. Results also revealed that psychological flexibility and mindfulness accounted for unique variance in all 4 measures of distress. These findings suggest that mindfulness and psychological flexibility are interrelated but not redundant constructs and that both constructs are important for understanding the onset and maintenance of somatization, depression, anxiety, and general distress.
The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid ...conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and nonalcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold. Herein, we report the discovery of 1 (tropifexor, LJN452), a novel and highly potent agonist of FXR. Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC.
The PTOLEMY project aims to develop a scalable design for a Cosmic Neutrino Background (CNB) detector, the first of its kind and the only one conceived that can look directly at the image of the ...Universe encoded in neutrino background produced in the first second after the Big Bang. The scope of the work for the next three years is to complete the conceptual design of this detector and to validate with direct measurements that the non-neutrino backgrounds are below the expected cosmological signal. In this paper we discuss in details the theoretical aspects of the experiment and its physics goals. In particular, we mainly address three issues. First we discuss the sensitivity of PTOLEMY to the standard neutrino mass scale. We then study the perspectives of the experiment to detect the CNB via neutrino capture on tritium as a function of the neutrino mass scale and the energy resolution of the apparatus. Finally, we consider an extra sterile neutrino with mass in the eV range, coupled to the active states via oscillations, which has been advocated in view of neutrino oscillation anomalies. This extra state would contribute to the tritium decay spectrum, and its properties, mass and mixing angle, could be studied by analyzing the features in the beta decay electron spectrum.
Objective:
The authors used an adoption study design to investigate environmental influences on risk for psychopathology in adolescents with depressed parents.
Method:
Participants were 568 adopted ...adolescents ascertained through large adoption agencies, 416 nonadopted adolescents ascertained through birth records, and their parents. Clinical interviews with parents and adolescents were used to determine lifetime DSM-IV-TR diagnoses of major depressive disorder, oppositional defiant disorder, conduct disorder, attention deficit hyperactivity disorder (ADHD), and substance use disorders in adolescents and major depression in mothers and fathers. Effects of parental depression (either parent with major depression, maternal major depression, and paternal major depression) on adolescent psychopathology were tested in nonadopted and adopted adolescents separately, and interactive effects of parental depression and adoption status were tested.
Results:
Either parent having major depression and a mother having major depression were associated with a significantly greater risk for major depression and disruptive behavior disorders in both nonadopted and adopted adolescents. Paternal depression did not have a main effect on any psychiatric disorder in adolescents and, with one exception (ADHD in adopted adolescents), did not predict significantly greater likelihoods of disorders in either nonadopted or adopted adolescents.
Conclusions:
Maternal depression was an environmental liability for lifetime diagnoses of major depression and disruptive disorders in adolescents. Paternal depression was not associated with an increased risk for psychopathology in adolescents.
The present cross-sectional study examined whether self-concealment was associated with general psychological distress, somatization, depression, and anxiety among Asian American, Black American, and ...White American college students in the U.S., and whether psychological inflexibility partially explains these associations. Participants (N = 991, 77% female, age range = 16–60 years) completed self-report measures of interest online. Results revealed the relations between self-concealment and the four distress variables in each ethnic group and suggested that these relations were explained partially through psychological inflexibility. Future research should examine this model among subpopulations of these ethnic groups, as well as the influence of various cultural variables.
•Self-concealment (SC) is a well-recognized maladaptive psychological process.•SC was known to be associated with various distress variables•Asian American and Black Americans are understudied groups in SC research•The present study revealed the associations between SC and distress in these understudied groups•Psychological inflexibility partially explained these associations.
Objective The aim of the Prospective Observational Trial to Optimize Pediatric Health in IUGR Study was to evaluate the optimal management of fetuses with an estimated fetal weight less than the 10th ...centile. The objective of this secondary analysis was to describe the role of the cerebroplacental ratio (CPR) in the prediction of adverse perinatal outcome. Study Design More than 1100 consecutive singleton pregnancies with intrauterine growth restriction (IUGR) were recruited over 2 years at 7 centers, undergoing serial sonographic evaluation including multivessel Doppler measurement. CPR was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Results Data for CPR calculation was available in 881 cases, which was performed at a mean gestational age of 33 weeks (interquarile range, 28.7–35.9). Of the 146 cases with CPR less than 1, 18% (n = 27) had an adverse perinatal outcome. This conferred an 11-fold increased risk (odds ratio, 11.7; P < .0001) when compared with cases with normal CPR (2%; 14 of 735). An abnormal CPR was present in all 3 cases of mortality. Prediction of adverse outcomes was comparable when using all definitions of abnormal CPR. Conclusion Irrespective of the CPR calculation used, brain sparing is significantly associated with an adverse perinatal outcome in IUGR. This adds further weight to integrating CPR evaluation into the clinical assessment of IUGR pregnancies. The impact of this finding on long-term neurodevelopmental outcomes in this patient cohort is underway.
Crystal calorimeters have a long history of pushing the frontier on high-resolution electromagnetic (EM) calorimetry for photons and electrons. We explore in this paper major innovations in collider ...detector performance that can be achieved with crystal calorimetry when longitudinal segmentation and dual-readout capabilities are combined with a new high EM resolution approach to Particle Flow in multi-jet events, such as e+e+→HZ events in all-hadronic final-states at Higgs factories. We demonstrate a new technique for pre-processing π0 momenta through combinatoric di-photon pairing in advance of applying jet algorithms. This procedure significantly reduces π0 photon splitting across jets in multi-jet events. The correct photon-to-jet assignment efficiency improves by a factor of about 3 when the EM resolution is improved from 15 to 3%/ E. In addition, the technique of bremsstrahlung photon recovery significantly improves electron momentum measurements. A high EM resolution calorimeter increases the Z boson recoil mass resolution in Higgstrahlung events for decays into electron pairs to 80% of that for muon pairs. We present the design and optimization of a highly segmented crystal detector concept that achieves the required energy resolution of 3%/ E, and a time resolution better than 30 ps providing exceptional particle identification capabilities. We demonstrate that, contrary to previous detector designs that suffered from large neutral hadron resolution degradation from one interaction length of crystals in front of a sampling hadron calorimeter, the implementation of dual-readout on crystals permits to achieve a resolution better than 30%/ E⊕2% for neutral hadrons. Our studies find that the integration of crystal calorimetry into future Higgs factory collider detectors can open new perspectives by yielding the highest level of combined EM and neutral hadron resolution in the PFA paradigm.